AJP - Lung Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Lung Cell Mol Physiol (June 10, 2002). doi:10.1152/ajplung.00467.2001
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
283/4/L830    most recent
00467.2001v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hippenstiel, S.
Right arrow Articles by Suttorp, N.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Hippenstiel, S.
Right arrow Articles by Suttorp, N.

Articles in PresS, published online ahead of print June 10, 2002
Am J Physiol Lung Cell Mol Physiol, 10.1152/ajplung.00467.2001
Submitted on December 6, 2001
Accepted on May 30, 2002

RHO PROTEIN INACTIVATION INDUCED APOPTOSIS OF CULTURED HUMAN ENDOTHELIAL CELLS

Stefan Hippenstiel1*, Bernd Schmeck1, Philippe Dje N'Guessan1, Joachim Seybold1, Matthias Krull1, Klaus Preissner1, Christoph V. Eichel-Streiber1, and Norbert Suttorp1

1 Departement of Internal Medicine, Charite, Humboldt-University, Berlin, Germany

* To whom correspondence should be addressed. E-mail: stefan.hippenstiel{at}charite.de.

Small GTP-binding Rho-GTPases regulate important signaling pathways in endothelial cells, but little is known about their role in endothelial cell apoptosis. Clostridial cytotoxins specifically inactivate GTPases by glucosylation [Clostridium difficile toxin B-10463 (TcdB-10463), C. difficile toxin B-1470 (TcdB-1470)] or ADP-ribosylation (C. botulinum C3-toxin). Exposure of human umbilical cord vein endothelial cells (HUVEC) to TcdB-10463 which inhibits RhoA/Rac1/Cdc42 or to C3-toxin which inhibits RhoA/B/C resulted in apoptosis, while inactivation of Rac1/Cdc42 with TcdB-1470 was without effect suggesting that Rho-inhibition was responsible for endothelial apoptosis. Disruption of endothelial microfilaments as well as inhibition of p160ROCK did not induce endothelial apoptosis. Exposure to TcdB-10463 resulted in activation of caspase 9 and 3 but not caspase 8 in HUVEC. Moreover, Rho-inhibition reduced expression of anti-apoptotic Bcl-2 and Mcl-1, increased pro-apoptotic Bid, but had no effect on Bax or FLIP protein levels. Caspase 3-activity and apoptosis induced by TcdB-10463 were abolished by cAMP elevation. In summary, inhibition of Rho in endothelial cells activates caspase 9- and 3-dependent apoptosis which can be antagonized by cAMP-elevation.




This article has been cited by other articles:


Home page
 Infect. Immun.Home page
K. Heine, S. Pust, S. Enzenmuller, and H. Barth
ADP-Ribosylation of Actin by the Clostridium botulinum C2 Toxin in Mammalian Cells Results in Delayed Caspase-Dependent Apoptotic Cell Death
Infect. Immun., October 1, 2008; 76(10): 4600 - 4608.
[Abstract] [Full Text] [PDF]

Home page
 J Med MicrobiolHome page
R. Gerhard, S. Nottrott, J. Schoentaube, H. Tatge, A. Olling, and I. Just
Glucosylation of Rho GTPases by Clostridium difficile toxin A triggers apoptosis in intestinal epithelial cells
J. Med. Microbiol., June 1, 2008; 57(6): 765 - 770.
[Abstract] [Full Text] [PDF]

Home page
 J. Dent. Res.Home page
J. Zahlten, B. Riep, F.C. Nichols, C. Walter, B. Schmeck, J.-P. Bernimoulin, and S. Hippenstiel
Porphyromonas gingivalis Dihydroceramides Induce Apoptosis in Endothelial Cells
J. Dent. Res., July 1, 2007; 86(7): 635 - 640.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
L. Yin, K.-i. Morishige, T. Takahashi, K. Hashimoto, S. Ogata, S. Tsutsumi, K. Takata, T. Ohta, J. Kawagoe, K. Takahashi, et al.
Fasudil inhibits vascular endothelial growth factor-induced angiogenesis in vitro and in vivo
Mol. Cancer Ther., May 1, 2007; 6(5): 1517 - 1525.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
J. Huelsenbeck, S. Dreger, R. Gerhard, H. Barth, I. Just, and H. Genth
Difference in the Cytotoxic Effects of Toxin B from Clostridium difficile Strain VPI 10463 and Toxin B from Variant Clostridium difficile Strain 1470
Infect. Immun., February 1, 2007; 75(2): 801 - 809.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
P. D. N'Guessan, M. O. Etouem, B. Schmeck, A. C. Hocke, S. Scharf, K. Vardarova, B. Opitz, A. Flieger, N. Suttorp, and S. Hippenstiel
Legionella pneumophila-induced PKC{alpha}-, MAPK-, and NF-{kappa}B-dependent COX-2 expression in human lung epithelium
Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L267 - L277.
[Abstract] [Full Text] [PDF]

Home page
 Integr Cancer TherHome page
M. F. McCarty and K. I. Block
Preadministration of High-Dose Salicylates, Suppressors of NF-{kappa}B Activation, May Increase the Chemosensitivity of Many Cancers: An Example of Proapoptotic Signal Modulation Therapy.
Integr Cancer Ther, September 1, 2006; 5(3): 252 - 268.
[Abstract] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
B. Schmeck, S. Huber, K. Moog, J. Zahlten, A. C. Hocke, B. Opitz, S. Hammerschmidt, T. J. Mitchell, M. Kracht, S. Rosseau, et al.
Pneumococci induced TLR- and Rac1-dependent NF-{kappa}B-recruitment to the IL-8 promoter in lung epithelial cells
Am J Physiol Lung Cell Mol Physiol, April 1, 2006; 290(4): L730 - L737.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
B. A. Carneiro, J. Fujii, G. A. C. Brito, C. Alcantara, R. B. Oria, A. A. M. Lima, T. Obrig, and R. L. Guerrant
Caspase and Bid Involvement in Clostridium difficile Toxin A-Induced Apoptosis and Modulation of Toxin A Effects by Glutamine and Alanyl-Glutamine In Vivo and In Vitro
Infect. Immun., January 1, 2006; 74(1): 81 - 87.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
H. He, J. Pannequin, J.-P. Tantiongco, A. Shulkes, and G. S. Baldwin
Glycine-extended gastrin stimulates cell proliferation and migration through a Rho- and ROCK-dependent pathway, not a Rac/Cdc42-dependent pathway
Am J Physiol Gastrointest Liver Physiol, September 1, 2005; 289(3): G478 - G488.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Microbiol. Rev.Home page
D. E. Voth and J. D. Ballard
Clostridium difficile Toxins: Mechanism of Action and Role in Disease
Clin. Microbiol. Rev., April 1, 2005; 18(2): 247 - 263.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
B. Schmeck, R. Gross, P. D. N'Guessan, A. C. Hocke, S. Hammerschmidt, T. J. Mitchell, S. Rosseau, N. Suttorp, and S. Hippenstiel
Streptococcus pneumoniae-Induced Caspase 6-Dependent Apoptosis in Lung Epithelium
Infect. Immun., September 1, 2004; 72(9): 4940 - 4947.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
H. Ikeda, K. Nagashima, M. Yanase, T. Tomiya, M. Arai, Y. Inoue, K. Tejima, T. Nishikawa, M. Omata, S. Kimura, et al.
Involvement of Rho/Rho kinase pathway in regulation of apoptosis in rat hepatic stellate cells
Am J Physiol Gastrointest Liver Physiol, November 1, 2003; 285(5): G880 - G886.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
C. I. Dubreuil, M. J. Winton, and L. McKerracher
Rho activation patterns after spinal cord injury and the role of activated Rho in apoptosis in the central nervous system
J. Cell Biol., July 21, 2003; 162(2): 233 - 243.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 2002 by the American Physiological Society.